Pain-alleviating composition



United States Patent 3,278,379 PAlN-ALLEVIATING COMPOSITION Leo Manson,Roslyn, Pa., assignor to Edgewood Laboratories, Inc., Philadelphia, Pa.,a corporation of Pennsylvania No Drawing. Filed Oct. 4, 1963, Ser. No.313,792 The portion of the term of the patent subsequent to Jan. 30,1979, has been disclaimed Claims. (Cl. 167-65) This invention relates toa therapeutically-active composition for internal administration, and itparticularly relates to a composition of the aforesaid type which ishighly effective in the alleviation of peripheral pain and irritation.

This application is a continuation-in-part of co-pending applicationSerial No. 137,003, filed September 11, 1961 and now abandoned, saidapplication Serial No. 137,003 having itself been a continuation-in-partof application Serial No. 734,110, which was filed May 9, 1958 andissued as US. Patent No. 3,019,165 on January 30, 1962.

The present invention basically comprises a composition wherein theessential therapeutically-active components, similarly to thecompositions disclosed in the aforementioned co-pending application, are(1) an analgesic such as a salicylate or its functional equivalents, (2)para aminobenzoic acid or its metal salts including the salts of thealkaline metals such as sodium and potassium; alkaline earth metals suchas calcium and barium; magnesium, aluminum, iron, tin, antimony, etc.,and (3) an antihistamine.

The essential factor in the composition is the relative proportions ofthe three therapeutically active components. When these proportions arewithin a certain range, there is a synergistic reaction which leads tocompletely unexpected and novel results whereby the pain-alleviatingeffect is greatly enchanced while deleterious side effects are almostentirely eliminated.

In the aforementioned co-pending application, the essential relativeproportions of the active components were set forth as being about 12parts by weight of the analgesic, about 3 parts by Weight of the paraaminobenzoic acid or its salts and about 0.24-2 parts by Weight of theantihistamine. It has now been discovered, however, that certainantihistamines may be effectively utilized in the above composition atconcentrations lower than 0.24 part by weight, specifically at aconcentration of not less than 0.04 but less than 0.24 part by Weight.

Among the antihistaminically-active compounds which are effective at theaforesaid lower concentrations, particularly outstanding are pyridinesand pyridine maleates having a tertiary amino ethyl group attached to anonreactive cyclic ring through either an oxygen or carbon atom.Examples of this type of compound are 2[u-(2-dimethylaminoethyl) benzyl]pyridine and pyridine maleate (prophenpyridamine and prophenpyridaminemaleate), both in the halogenated and unhalogenated form,2-[pchloro-u-(Z-dimethylaminoethoxy) benzyl] pyridine maleate and di 2{1[2 (2 dimethylaminoethyl) 3-indenyl] ethyl} pyridine maleate.

A specific composition embodying the present invention comprises atablet containing as the therapeutically-active components about 300-325mg. of acetyl salicylic acid, about 75 mg. of para aminobenzoic acid andabout 1 mg. of di-2{1[2-(Z-dimethylaminoethyl)-3-indenyl] ethyl}pyridine maleate. This composition has been found to be highly effectivein the relief of peripheral pain, such as may result from sunburn orother causes, while being ice substantially free of such side effects asnausea, vomiting, anorexia, fever, dermatitis medicamentosa, etc.

The present composition may include various diluents, fillers,neutralizers, etc. such as are common in the art. For example, it mayinclude among other ingredients bonding agents such as starch,neutralizing agents such as MgCO and diluents such as lactose, stearate,acacia, glucose, dextrose, etc.

For the relief of peripheral pain and irritation, the tablets of thepresent invention are preferably orally administered in a dosage ofabout 1-2 tablets every 3, 4 or 6 hours.

To avoid the undesirable effects of sunburn, the initial dose ispreferably 1 tablet taken not less than 1 hour prior to exposure to thesun followed by 1 tablet in successive doses at four hour intervals. Thesame dosage may be used to alleviate pain and edema by after-treatmentof sunburn or other burns.

Obviously many modifications and variations of the present invention arepossible in the light of the above teachings. It is, therefore, to beunderstood that within the scope of the appended claims, the inventionmay be practiced otherwise than as specifically described.

The invention claimed is:

1. A pharmaceutical composition consisting essentially of about 12 partsby weight acetyl salicylic acid, about 3 parts by weight paraaminobenzoic acid and an amount not less than about 0.04 but less than0.24 part by weight of an antihistaminically-active compound selectedfrom the group consisting of pyridines and pyridine maleates having atertiary amino ethyl group attached to a nonreactive cyclic ring throughan atom selected from the group consisting of oxygen and carbon atoms.

2. A pharmaceutical composition consisting essentially of about 12 partsby weight acetyl salicylic acid, about 3 parts by weight paraaminobenzoic acid and an amount not less than about 0.04 but less than0.24 part by weight of 2[tx-(Z-dimethylaminoethyl) benzyl] pyridine.

3. A pharmaceutical composition consisting essentially of about 12 partsby weight acetyl salicylic acid, about 3 parts by weight paraaminobenzoic acid and an amount not less than about 0.04 but less than0.24 part by weight of 2[u-(2-dimethylaminoethyl) benzyl] pyridinemaleate.

4. A pharmaceutical composition consisting essentially of about 12 partsby weight acetyl salicylic acid, about 3 parts by weight paraaminobenzoic acid and an amount not less than about 0.04 but less than0.24 part by Weight of 2-p-chloro-a(Z-dimethylaminoethoxy) benzyl]pyridine maleate.

5. A pharmaceutical composition consisting essentially of about 12 partsby Weight acetyl salicylic acid, about 3 parts by weight paraaminobenzoic acid and an amount not less than about 0.04 but less than024 part by weight of di-2{1[2-(Z-dimethylaminoethyl)-3-indenyl] ethyl}pyridine maletate.

References Cited by the Examiner UNITED STATES PATENTS 3,019,165 1/1962Mansor 167-65 3,076,804 2/1963 Huebner 260240 OTHER REFERENCES MerckIndex, 7th Ed. (1960), Merck & Co., Rahway, New Jersey, pp. 878-9.

JULIAN S. LEVITT, Primary Examiner.

MARTIN I COHEN, Assistant Examiner.

2. A PHARMACEUTICAL COMPOSITION CONSISTING ESSENTIALLY OF ABOUT 12 PARTSBY WEIGHT ACETYL SALICYLIC ACID, ABOUT 3 PARTS BY WEIGHT PARAAMINOBENZOIC ACID AND AN AMOUNT NOT LESS THAN ABOUT 0.04 BUT LESS THAN0.24 PART BY WEIGHT OF 2(A-(2-DIMETHYLAMINOETHYL) BENZYL) PYRIDINE.